Efficacy of an intermittent energy restriction diet in a primary care setting.

PURPOSE: Intermittent energy restriction (IER) is a popular weight loss (WL) strategy; however, its efficacy in clinical practice remains unknown. The present study compared the effects of IER compared to continuous energy restriction (CER) on WL and cardiometabolic risk factors in primary care. METHODS: A (self-selected) cohort study was conducted at the Rotherham Institute for Obesity (RIO), a primary care-based weight management service. 197(24% male) obese patients volunteered to participate and selected their diet group. IER participants (n = 99) consumed ~ 2600 kJ for two days/week. CER participants (n = 98) restricted their diet by ~ 2100 kJ/day below estimated requirements. Both interventions were delivered alongside RIO standard care. Changes in anthropometry and cardiometabolic disease risk markers (fasting biochemistry and blood pressure) were assessed after a 6-month intervention period and then participants were followed up again 6 months later (month 12). RESULTS: 27 IER patients (27%) and 39 CER patients (40%) completed the 6-month weight loss phase. Among completers, mean (SEM) WL was greater in the IER group at 6 months (5.4 ± 1.1% versus 2.8 ± 0.6%; p = 0.01), as were reductions in fat mass (p < 0.001) and improvements in systolic blood pressure (p < 0.001). Fasting insulin (p = 0.873) and diastolic blood pressure (p = 0.701) were reduced similarly in both groups. However, in the IER group, changes in anthropometry and blood pressure in the IER group had reverted to baseline by 12-month follow-up, whilst the CER group maintained weight loss but showed an increase in blood pressure. CONCLUSIONS: Among completers, IER resulted in superior short-term changes in anthropometry and some cardiometabolic risk factors. However, rates of attrition and weight regain were higher compared with standard care, providing important insights in the implementations of IER within a "real-life" NHS setting. TRIAL REGISTRATION NUMBER: ISRCTN31465600.

Elevated high density lipoprotein cholesterol and low grade systemic inflammation is associated with increased gut permeability in normoglycemic men.

BACKGROUND & AIMS: Serum lipids and lipoproteins are established biomarkers of cardiovascular disease risk that could be influenced by impaired gut barrier function via effects on the absorption of dietary and biliary cholesterol. The aim of this study was to examine the potential relationship between gut barrier function (gut permeability) and concentration of serum lipids and lipoproteins, in an ancillary analysis of serum samples taken from a previous study. METHODS AND RESULTS: Serum lipids, lipoproteins and functional gut permeability, as assessed by the percentage of the urinary recovery of 51Cr-labelled EDTA absorbed within 24 h, were measured in a group of 30 healthy men. Serum lipopolysaccharide, high sensitivity C-reactive protein and interleukin-6 were also measured as markers of low-grade inflammation. The group expressed a 5-fold variation in total gut permeability (1.11-5.03%). Gut permeability was unrelated to the concentration of both serum total and low density lipoprotein (LDL)-cholesterol, but was positively associated with serum high density lipoprotein (HDL)-cholesterol (r = 0.434, P = 0.015). Serum HDL-cholesterol was also positively associated with serum endotoxaemia (r = 0.415, P = 0.023). CONCLUSION: The significant association between increased gut permeability and elevated serum HDL-cholesterol is consistent with the role of HDL as an acute phase reactant, and in this situation, potentially dysfunctional lipoprotein. This finding may have negative implications for the putative role of HDL as a cardio-protective lipoprotein.

Reverse Monte Carlo reconstruction algorithm for discrete electron tomography based on HAADF-STEM atom counting.

In this paper, we propose an algorithm to obtain a three-dimensional reconstruction of a single nanoparticle based on the method of atom counting. The location of atoms in three dimensions has been successfully performed using simulations of high-angle-annular-dark-field images from only three zone-axis projections, [110], [310] and [211], for a face-centred cubic particle. These three orientations are typically accessible by low-tilt holders often used in high-performance scanning transmission electron microscopes.

Influence of the tolerability of vinegar as an oral source of short-chain fatty acids on appetite control and food intake.

BACKGROUND: Vinegar is promoted as a natural appetite suppressant, based on previous reports that vinegar ingestion significantly increases subsequent satiety. However there are concerns about the appropriateness and safety of this advice, and it is unclear if poor product palatability may explain previously published effects on appetite. OBJECTIVE: To investigate if vinegar palatability and tolerability have a role in suppressing appetite and food intake in two sequential and related acute human feeding studies. SUBJECTS AND METHODS: Healthy, young, normal weight unrestrained eaters were recruited to Study 1 (n=16), an acute feeding study supplying vinegar within both palatable and unpalatable drinks alongside a mixed breakfast in comparison to a non-vinegar control; and to Study 2 (n=14), a modified sham feeding study (taste only without ingestion) comparing vinegar to a non-vinegar control following a milkshake preload. Both studies were a randomized crossover balanced design for the assessment of appetite, energy intake and glycaemic response. RESULTS: In Study 1, ingestion of vinegar significantly reduced quantitative and subjective measures of appetite, which were accompanied by significantly higher nausea ratings, with unpalatable treatment having the greatest effect. Significant correlations between palatability ratings and appetite measures were found. In Study 2, orosensory stimulation with vinegar did not influence subsequent subjective or quantitative measures of appetite compared with control. CONCLUSIONS: These studies indicate that vinegar ingestion enhances satiety whereas orosensory stimulation alone does not, and that these effects are largely due to poor tolerability following ingestion invoking feelings of nausea. On this basis the promotion of vinegar as a natural appetite suppressant does not seem appropriate.

Increased intestinal permeability to oral chromium (51 Cr) -EDTA in human Type 2 diabetes.

OBJECTIVE: In animal models of obesity and Type 2 diabetes, permeability of the intestine is increased because of impairment of tight junction proteins, allowing translocation of bacterial endotoxin and resulting in low-grade systemic inflammation. This has yet to be demonstrated in humans. The objective of this study was the demonstration of increased intestinal permeability in human Type 2 diabetes. METHODS: We examined intestinal permeability using chromium ((51) Cr)-EDTA urinary recovery in twenty well-controlled men with Type 2 diabetes compared with control subjects matched for age, gender and BMI. RESULTS: Intestinal permeability was significantly increased (P = 0.002) in the diabetic group and was correlated to increased levels of systemic inflammatory markers high-sensitivity C-reactive protein (r = 0.694, P = 0.001), interleukin 6 (r = 0.548, P = 0.012) and tumour necrosis factor alpha (r = 0.564, P = 0.010). CONCLUSION: This is the first demonstration that increased intestinal permeability may be a feature of human Type 2 diabetes.

Long-term effects of clinical interventions on nutritional status in patients with chronic pancreatitis - A systematic review.

BACKGROUND AND AIMS: Malnutrition in chronic pancreatitis is complex and multifactorial, with malabsorption, pain, toxic dependencies and co-morbidities, such as diabetes, each playing a role. The aims of this systematic review were to assess the impact of nutritional intervention on markers of nutritional status in this complex patient group. MATERIALS AND METHODS: A systematic review of EMBASE and PubMed was carried out in February 2020, identifying 2620 articles. After screening to exclude those reporting short term changes (less than 3 months), with only one data point, or in the wrong population, eight papers were selected for analysis. RESULTS: Seven studies documented the impact of a nutritional intervention, one was an observational study only. Overall, studies were limited by predominantly retrospective designs, heterogenous populations and poor control of potentially confounding variables. Data could not be combined due to variability in reporting methods. All studies exploring nutritional intervention, whether that consisted of advice by a specialist dietitian, dose escalation of pancreatic enzymes, oral nutritional supplements or enteral feeding, demonstrated improved body weight and pain control, whereas patients who did not receive an intervention deteriorated nutritionally. CONCLUSION: Patients with chronic pancreatitis benefit from nutritional intervention. Further work is required to explore the impact of nutritional intervention on body composition and functional outcomes.

Resistant Starch Production and Glucose Release from Pre-Prepared Chilled Food: The SPUD Project.

With an increasing prevalence of diabetes worldwide, effective dietary strategies for blood glucose control are crucial. As carbohydrates make up approximately 50% of the diet, it is neither practical nor advisable to avoid them altogether. Most of the carbohydrate in the diet is derived from starch, found in potatoes, pasta, rice and bread. These foods are often processed in some way before consumption, yet little is known about the effects processing, such as chilling and reheating, has on the glycaemic response, particularly when the food is consumed in the context of a mixed meal. This article introduces the SPUD project, a BBSRC DRINC-funded initiative. Taking the potato as the model carbohydrate, this project will investigate, via in vitro and in vivo studies, the effects of domestic food processing techniques on the glycaemic response. A final study, utilising intrinsically labelled potato and a dual stable isotope methodology, will model glucose flux data to determine the underlying mechanisms of action.

Long-term changes in nutritional status and body composition in patients with malignant pancreatic disease - A systematic review.

BACKGROUND AND AIMS: Patients with pancreatic cancer often experience significant deterioration in nutritional status over time. Malnutrition is complex and multifactorial, with malabsorption, pain, toxic dependencies, co-morbidities and malignant processes all playing a role. The aims of this systematic review were to assess nutritional changes over time and identify tolerance of nutritional intervention, thus identifying potential areas for further research to improve patient outcomes. MATERIALS AND METHODS: A systematic review of MEDLINE, EMBASE and PubMed was carried out in February 2020, identifying 2620 articles. After screening to exclude those reporting short-term measures, with only one data point, or in the wrong population, thirteen papers were selected for analysis (four trials in neo-adjuvant treatment, five in populations undergoing palliative treatment for pancreatic cancer, and four in mixed populations undergoing pancreatic resection). RESULTS: Overall, studies were limited by predominantly retrospective designs, and poor control of potentially confounding variables. Meta-analysis could not be performed due to heterogenicity in study design and reporting methods. Surgery in mixed cohorts did not appear to result in weight loss. Only one small intervention study was identified. Patients with pancreatic cancer experienced a decline in nutritional status, with 44-63% of patients undergoing neoadjuvant chemotherapy having low muscle mass prior to starting treatment. CONCLUSION: There is a paucity of data regarding nutritional intervention in pancreatic cancer. Future work should include the use of validated functional and clinical assessment tools to further explore the impact of nutritional intervention, and the relationship between nutritional status and outcome.

Lagged recovery of fish spatial distributions following a cold-water perturbation.

Anomalous local temperature and extreme events (e.g. heat-waves) can cause rapid change and gradual recovery of local environmental conditions. However, few studies have tested whether species distribution can recover following returning environmental conditions. Here, we tested for change and recovery of the spatial distributions of two flatfish populations, American plaice (Hippoglossoides platessoides) and yellowtail flounder (Limanda ferruginea), in response to consecutive decreasing and increasing water temperature on the Grand Bank off Newfoundland, Canada from 1985 to 2018. Using a Vector Autoregressive Spatiotemporal model, we found the distributions of both species shifted southwards following a period when anomalous cold water covered the northern sections of the Grand Bank. After accounting for density-dependent effects, we observed that yellowtail flounder re-distributed northwards when water temperature returned and exceeded levels recorded before the cold period, while the spatial distribution of American plaice has not recovered. Our study demonstrates nonlinear effects of an environmental factor on species distribution, implying the possibility of irreversible (or hard-to-reverse) changes of species distribution following a rapid change and gradual recovery of environmental conditions.

Resistant starch improves insulin sensitivity in metabolic syndrome.

AIMS: Diets rich in non-viscous fibre are linked to a reduced risk of both diabetes and cardiovascular disease; however, the mechanism of action remains unclear. This study was undertaken to assess whether chronic consumption of this type of fibre in individuals with the metabolic syndrome would improve insulin sensitivity via changes in ectopic fat storage. METHODS: The study was a single-blind, randomized, parallel nutritional intervention where 20 insulin resistant subjects consumed either the fibre supplement (resistant starch) (40 g/day) or placebo supplement (0 g/day) for 12 weeks. Insulin sensitivity was measured by euglycaemic-hyperinsulinaemic clamp and ectopic fat storage measured by whole-body magnetic resonance spectroscopy. RESULTS: Resistant starch consumption did not significantly affect body weight, fat storage in muscle, liver or visceral depots. There was also no change with resistant starch feeding on vascular function or markers of inflammation. However, in subjects randomized to consume the resistant starch, insulin sensitivity improved compared with the placebo group (P = 0.023). Insulin sensitivity correlated significantly with changes in waist circumference and fat storage in tibialis muscle and to a lesser extent to visceral-to-subcutaneous abdominal adipose tissue ratio. CONCLUSION: Consumption of resistant starch improves insulin sensitivity in subjects with the metabolic syndrome. Unlike in animal models, diabetes prevention does not appear to be directly related to changes in body adiposity, blood lipids or inflammatory markers. Further research to elucidate the mechanisms behind this change in insulin sensitivity in human subjects is required.

Impact of restraint and disinhibition on PYY plasma levels and subjective feelings of appetite.

The impact of eating behaviours on circulating levels of appetite-regulating hormones remains largely unknown. The aims of this study were to assess the role of restraint and disinhibition on fasting/postprandial peptide YY (PYY) plasma levels and subjective feelings of appetite in normal-weight individuals and to determine whether the effect was energy load dependent. 33 participants (12 men) were classified as restrained/unrestrained and low/high in disinhibition based on Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint/disinhibition on PYY plasma levels and feelings of appetite was measured, after a 500kcal and 1000kcal breakfast, using a randomised crossover design. Restraint did not impact on either fasting or postprandial PYY plasma levels, but participants with high disinhibition had a tendency towards a blunted postprandial PYY response. Moreover, restrained eaters reported lower ratings of prospective food consumption postprandially, and a tendency towards higher fullness/lower hunger. In conclusion, circulating PYY is unaffected by restrained eating behaviour, despite being associated with increased fullness and reduced hunger in the fed state. High levels of disinhibition tend to be associated with a blunted PYY response and this may contribute towards the susceptibility to overconsumption and increased risk of weight gain characteristic of this trait.

Effects of restrained eating behaviour on insulin sensitivity in normal-weight individuals.

Restrained eating behaviour has been linked to abnormalities in metabolic and endocrine functions. However, the impact of restraint on fasting insulin and glucose plasma levels and insulin sensitivity remains controversial. Moreover, the few postprandial studies to date are limited by an inappropriate sampling time frame and a low "net" energy and carbohydrate load. The aims of this study are to assess the role of dietary restraint on fasting and postprandial plasma levels of insulin, glucose, triacylglycerol (TAG) and non esterified fatty acids (NEFA) in healthy volunteers with a normal and stable body weight and to determine whether the effect of restraint on the plasma levels of the previous hormones/metabolites is load dependent. Normal-weight participants (21 women and 12 men) were classified as restrained/unrestrained based on the restraint scale of the Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint on the plasma levels of different hormones/metabolites was measured, in response to a 500 kcal and 1000 kcal breakfast, using a randomised crossover design. Restraint was associated with lower fasting insulin plasma levels (P<0.05) and a lower insulin (P<0.015) and glucose (P<0.05) plasma levels in the postprandial state, but did not impact on TAG or NEFA. Moreover, restrained eaters showed a better fasting (P<0.05) and postprandial insulin sensitivity (P<0.01). Restrained eating behaviour has, therefore, a significant impact on both fasting and postprandial glucose metabolism, being associated with increased insulin sensitivity. These findings suggest the need for adjusting for restraint level in studies where glucose metabolism is a major outcome.

A study in the computation time required for the inclusion of strain field effects in Bloch-wave simulations of TEM diffraction contrast images.

As transmission electron microscopy (TEM) imaging techniques continue to become more quantitative, interpretation of the experimental images demands that accurate image simulations be computed incorporating all important aspects of the image including: compositional, crystallographic and microscope effects, as well as contrast due to strain fields arising from stresses created by lattice misfit or defects. Incorporation of the effects of strain fields in the simulation of diffraction-contrast TEM images in the Bloch-wave formalism requires the integration of a system of first-order differential equations in order to modify the excitation amplitudes and produce contrast in the image. This integration is computationally demanding with the time for integration scaling as the cube of the number of beams included in the calculation. In order to investigate the computational requirements of the integration, a variety of numerical integration packages were evaluated with respect to timing and accuracy in the simulation of quantum dot, spherical inclusion and screw dislocation images. It was determined that a class of Adams-multistep methods can provide a decrease in computation time ranging from 2 to 4 as compared to the standard Runge-Kutta 4(5) approach depending on the simulation conditions.

On the role of the second-order derivative term in the calculation of convergent beam diffraction patterns.

The simulation of (scanning) transmission electron microscopy images and diffraction patterns is most often performed using the forward-scattering approximation where the second-order derivative term in z is assumed to be small with respect to the first-order derivative term in the modified Schrödinger equation. This assumption is very good at high incident electron energies, but breaks down at low energies. In order to study the differences between first- and second-order methods, convergent beam electron diffraction patterns were simulated for silicon at the [111] zone-axis orientation at 20 keV and compared using electron intensity difference maps and integrated intensity profiles. The geometrical differences in the calculated diffraction patterns could be explained by an Ewald surface analysis. Furthermore, it was found that solutions based on the second-order derivative equation contained small amplitude oscillations that need to be resolved in order to ensure numerical integration stability. This required the use of very small integration steps resulting in significantly increased computation time compared to the first-order differential equation solution. Lastly, the efficiency of the numerical integration technique is discussed.

Food perception and postprandial lipid metabolism.

The postprandial response to macronutrients in the diet, particularly carbohydrates and fats, underpins the detrimental changes in metabolism (impaired glucose tolerance or postprandial hyperlipaemia) and later pathology (insulin resistance, type 2 diabetes or atherosclerosis) associated with Westernised diets. Research has shown that in addition to what and how much we eat, eating behaviour in itself may be implicated in postprandial regulation. The process of ingestion stimulates cholinergic-vagal activity, irrespective of what is eaten, important in determining both the absorption and subsequent utilisation of nutrients but also potentially food intake through effects on hunger and satiety. Modifications in this aspect of physiology have the potential to influence all aspects of postprandial metabolism and subsequent disease risk in humans.

Enhanced metabolic cycling in subjects after colonic resection for ulcerative colitis.

Colonic resection leads to insulin resistance, but the mechanisms are unknown. We used an integrated approach to examine adipose tissue and skeletal muscle metabolism in patients lacking a colon. Ten healthy colectomized patients having undergone surgery for ulcerative colitis and 10 matched control subjects were studied with a hyperinsulinemic-euglycemic clamp to measure insulin sensitivity, an arteriovenous sampling meal tolerance study to measure postprandial substrate flux across adipose tissue and skeletal muscle, and adipose tissue and skeletal muscle biopsies to quantify the expression of genes involved in glucose and lipid metabolism. Colectomized subjects exhibited lower insulin sensitivity (homeostatic model assessment model, 33% reduction, P = 0.03; minimal model, 29% reduction, P = 0.05), elevated aldosterone (9-fold, P = 0.003), leptin (2.2-fold, P = 0.03), and an increased rate of nonesterified fatty acid and glycerol release from adipose tissue (P = 0.02) especially in the late postprandial period. The uptake of fatty acids into muscle was also significantly increased (P = 0.007), as were muscle CD36 and LPL mRNA expression compared with controls. In adipose tissue, hormone-sensitive lipase mRNA expression was increased (P = 0.015), whereas peroxisome proliferator-activated receptor-gamma expression was decreased (P = 0.02), as was that of CD36 (P = 0.001). In this study, alterations in fatty acid metabolism after colonic resection altered may have contributed to the impairment of insulin sensitivity.

The determination of the size and shape of buried InAs/InP quantum dots by transmission electron microscopy.

Bright-field, diffraction-contrast imaging in the transmission electron microscope has been applied to the determination of the diameter and height populations of a single layer of buried, pure, InAs/InP quantum dots (QDs). Plan-view diffraction contrast from the QDs was observed to increase significantly when the sample was tilted away from the [001] growth direction to near the [111] zone-axis orientation. This added contrast was a result of contributions to the displacement of atoms in a direction perpendicular to the electron beam arising from strain in the growth direction. Since the strain in the growth direction was about an order of magnitude larger than the strain perpendicular to the growth direction, as the sample is tilted away from the [001] zone-axis condition, the larger strain component increases the projected strain thereby increasing the QD contrast in the image. For the sample studied, both of the populations for the QD diameter and the image contrast were observed to be multimodal with the seven peaks in the contrast distribution correlating with seven distinct populations of QDs each differing in height by one monolayer (ML), from 3 to 9MLs. An analysis of the theoretically expected and experimentally observed standard deviations in the Gaussian fits to the QD diameter and height distributions provided an additional constraint in the selection of the optimal model for the multimodal distributions.

Prolonged effects of modified sham feeding on energy substrate mobilization.

BACKGROUND: Vagal stimulation in response to nutrients is reported to elicit an array of digestive and endocrine responses, including an alteration in postprandial lipid metabolism. OBJECTIVE: The objective of this study was to assess whether neural stimulation could alter hormone and substrate metabolism during the late postprandial phase, with implications for body fat mobilization. DESIGN: Vagal stimulation was achieved by using the modified sham feeding (MSF) technique, in which nutrients are chewed and tasted but not swallowed. Ten healthy subjects were studied on 3 separate occasions, 4 wk apart. Five hours after a high-fat breakfast (56 g fat), the subjects were given 1 of 3 test meals allocated in random order: water, a lunch containing a modest amount of fat (38 g), or MSF (38 g fat). Blood was collected for 3 h poststimulus for hormone and metabolite analyses. RESULTS: Plasma insulin and pancreatic polypeptide concentrations peaked at 250% and 209% of baseline concentrations within 15 min of MSF. The plasma glucose concentration increased significantly (P = 0.038) in parallel with the changes observed in the plasma insulin concentration. The nonesterified fatty acid concentration was significantly suppressed (P: = 0.006); maximum suppression occurred at a mean time of 114 min after MSF. This fall in nonesterified fatty acid was accompanied by a fall in the plasma glucagon concentration from 122 to 85 pmol/L (P = 0.018) at a mean time of 113 min after MSF. CONCLUSIONS: Effects on substrate metabolism after MSF in the postprandial state differ from those usually reported in the postabsorptive state. The effects of MSF were prolonged beyond the period of the cephalic response and these may be relevant for longer-term metabolic regulation.

Vagal stimulation exaggerates the inhibitory ghrelin response to oral fat in humans.

Ghrelin, the growth hormone secretagogue receptor ligand, is a key regulator of adiposity and food intake. However, the regulation of ghrelin in response to dietary fat intake remains largely unclear. Furthermore, cephalic elevation of ghrelin may influence fat absorption and postprandial lipaemia. Therefore, the aim of this study was to examine the effect of fat ingestion and vagal stimulation on the regulation of plasma ghrelin. Vagal stimulation was achieved by modified sham feeding (MSF). Eight healthy subjects (four male/four female) consumed a 50 g fat load on two separate occasions. On one occasion, the fat load was preceded by the MSF of a meal for 1 h. Blood, appetite and breath were analysed for 5 h postprandially.A 25% (S.E.M. 3.4) suppression in ghrelin concentration was observed after fat ingestion (P<0.001), without an increase in glucose or insulin. MSF in addition to oral fat enhanced ghrelin suppression further, as well as elevating plasma triacylglycerol (P<0.001) and reducing appetite (P<0.001). The fasting ghrelin concentration was inversely correlated with gastric half-emptying time (P=0.036). We conclude that ghrelin release may be influenced directly by both vagal stimulation and oral fat ingestion.